CN113908343B - Biomaterial with improved bending performance - Google Patents

Abstract

Aiming at the technical problems that the biological material is too soft after hydration, it is difficult to fully stretch, it is difficult to fit the defective tissue, and it is difficult to be sutured and fixed, the invention discloses a biological material with improved bending performance, including acellular bladder basement membrane UBM and acellular matrix , the UBM completely covers the acellular matrix, the thickness of the UBM is 0.05-0.2mm, and the acellular matrix includes small intestinal submucosa SIS, dermis, pericardium, amnion, and peritoneum. On the premise of not increasing the overall thickness of the biomaterial, different thicknesses of the UBM surface layer of the decellularized bladder basement membrane were introduced to improve and adjust the mechanical strength and softness of the biomaterial after hydration.

Description

A biomaterial with improved bending properties

technical field

The invention belongs to the field of tissue repair materials, in particular to a biological material with improved bending performance.

Background technique

Acellular matrix biomaterials are the development trend of soft tissue repair materials, and their application characteristics can induce "endogenous tissue regeneration": after implantation, the biological signals or degradation products contained in them can induce macrophages and stem cells around the repair area to actively , Rapid infiltration, growth, proliferation and secretion of its own extracellular matrix to replace the implant. With the growth of host tissue, ACTM gradually degrades, and the two are basically synchronized, and finally ACTM is completely replaced by host tissue. Acellular matrix biomaterials have been clinically used to replace meninges, pleura, abdominal wall fascia, etc., to strengthen the anastomotic stoma, to reconstruct the pelvic floor, to suspend the bladder, to stop bleeding from solid organ damage such as liver and spleen, and to hemostasis of various complex hernias and abdominal wall defects. Treatment such as abdominal wall defect with contamination, infection after implantation of synthetic mesh, secondary surgery for intestinal fistula, etc.

For patch products that need to be sutured and fixed when implanted into the human body, materials that are too soft are difficult to stretch when applied, and suture is more difficult; while materials that are too stiff cannot fit the wound for suturing; therefore, the stiffness of the patch is limited. Adjustment of one index has significant clinical significance. During the clinical application of biomaterials, it is inevitable that they will come into contact with blood or tissues in human tissues to cause hydration. Therefore, the evaluation of the stiffness of biomaterials after hydration is more in line with the needs of clinical reagents. At present, biomaterials are only good in flexibility when they are dry, and they are soft immediately after hydration, and are not easy to fit or suture and fix. This increases the difficulty of the doctor's operation and prolongs the operation time. Chinese invention patent CN107335097A attempts to add synthetic fibers between the material layers to improve the mechanical strength and flexibility of the material after hydration, but the degradation products of degradable synthetic fibers are acidic substances, which are not conducive to the healing of defective tissues; non-degradable synthetic fibers may Lead to material shrinkage, chronic erosion, pain and other problems.

Contents of the invention

Aiming at the technical problems that the biological material is too soft after hydration, it is difficult to fully stretch, it is difficult to fit the defective tissue, and it is difficult to be sutured and fixed, the present invention provides a biological material with improved bending performance. UBM surface layer of decellularized bladder basement membrane with different thicknesses to improve and adjust the mechanical strength and softness of the biomaterial after hydration.

To achieve the above object, the technical solution of the present invention is:

A biomaterial with improved bending properties, comprising decellularized bladder basement membrane UBM and an acellular matrix, the UBM completely covers the acellular matrix, the thickness of the UBM is 0.05-0.2mm, and the acellular matrix is Small intestinal submucosa SIS, pericardium, dermis, amniotic membrane, peritoneum, etc.

The bending length of the biological material is not reduced by more than 50% after 10 minutes of complete hydration.

The UBM is prepared from the mammalian bladder by mechanically removing the serosa, the muscular layer, the submucosa and the muscularis mucosae and then decellularized.

The SIS is prepared from the mammalian small intestine by mechanically removing the mucous membrane, the serosa layer and the muscular layer and then decellularized.

The biological material also includes drugs.

The drug is distributed between layers or on the surface, or between layers and on the surface, of the biological material by means of a medium. The interlayer is part of the interlayer or each interlayer.

The biological material takes the SIS as the middle layer, and the UBM as the upper and lower surface layers, and the upper and lower surface layers completely cover the middle layer to form a sandwich structure.

UBM can be a single-layer or multi-layer structure.

Each layer of the biological material is fixed by vacuum lamination.

The process parameters of the vacuum lamination are: the vacuum pressure is -50--760mmHg, and the action time is 0.5-72h.

Compared with the prior art, the present invention has the following advantages and positive effects due to the adoption of the above technical scheme:

In the present invention, UBM with a thickness range of 0.05-0.2mm is used as the surface layer of the biological material. After the biological material is hydrated, it can still maintain the stiffness of the material for a long time. slice fixed time. By changing the thickness of the UBM surface layer, the stiffness of the biomaterial after hydration can be further adjusted without increasing the overall thickness of the biomaterial.

Detailed ways

A biomaterial with improved bending performance proposed by the present invention will be further described in detail below in conjunction with specific examples. The advantages and features of the present invention will become clearer from the following description.

A biomaterial with improved bending properties, including decellularized bladder basement membrane UBM and acellular matrix, UBM is completely covered with acellular matrix, the thickness of UBM is 0.05-0.2mm, and the acellular matrix is porcine small intestinal submucosa, dermis, pericardium , amnion, peritoneum, etc.

The structure of the biomaterial is preferably UBM as the upper and lower surface layers, SIS as the middle layer, and the upper and lower surface layers completely cover the middle layer to form a sandwich structure.

The biomaterial layers are fixed by vacuum lamination.

The process parameters of vacuum lamination are: the vacuum pressure is -50~-760mmHg, and the action time is 0.5~72h.

The bending length of the biological material of the present invention is not reduced by more than 50% after being fully hydrated for 10 minutes.

UBM is made from the mammalian bladder by mechanical means to remove the serosa, muscular layer, submucosa, and muscularis mucosa after decellularization.

SIS is produced by decellularization of the mammalian small intestine after mechanical removal of the mucosa, serosa and muscularis.

Drugs can also be added to the biological material, and the drug is distributed between the layers or the surface of the biological material or between the layers and the surface by means of a medium.

Example 1

Select raw materials according to the following proportions to prepare biological materials:

Control substance: 8-layer SIS

Sample A: 6 layers of SIS + upper and lower surface layers of UBM, the thickness of the UBM surface layer is 0.05mm

Sample B: 6 layers of SIS + upper and lower surface layers of UBM, the thickness of the UBM surface layer is 0.1mm

Sample C: 6 layers of SIS + upper and lower surface layers of UBM, the thickness of the UBM surface layer is 0.2mm

The samples to be tested were made by vacuum lamination process.

Thickness test: Use a spiral thickness meter to test the prepared reference substance and samples, and randomly test 5 points for each batch of samples, and the results are the average value. There was no significant difference in the overall thickness of the materials in each group, and the results are shown in Table 1.

Gram weight: Use an analytical balance to test the weight per unit area of the prepared reference substance and samples. There was no significant difference in the weight per unit area of materials in each group, and the results are shown in Table 1.

Table 1 The thickness of the test sample and the results of the grammage per unit area

Sample thickness (mm) Weight per unit area (g/m²) Reference substance 0.25 143 Sample A 0.22 132 Sample B 0.30 147 Sample C 0.25 135

Bending length test method: refer to GB/T 18318.1-2009 Determination of the Bending Properties of Textiles Part 1: Inclined Plane Method. Take a material with a width of 1 cm and a length of 20 cm, and use the section method to measure the bending length and flexural strength of the unhydrated material. The material was completely submerged in normal saline at room temperature for 2 minutes and 10 minutes. After taking it out, the bending length and bending stiffness were measured again in the same way, and each sample was repeated 5 times to obtain the average value. The test results are shown in Table 2. Bending length is defined as the length of a rectangular specimen held at one end and suspended at the other end when it is bent to a specific angle under its own weight; flexural stiffness is defined as the ratio of the small bending moment change per unit width of the material to its corresponding curvature change.

Table 2 The test results of bending length and bending stiffness

From the results of bending length and bending stiffness in Table 2, it can be seen that the bending length of samples A, B, and C after hydration decreases by no more than 50% of that before hydration, that is to say, the surface layer of the present invention is UBM, and the UBM is completely covered The structure of the SIS, and the thickness of the UBM is in the range of 0.05-0.2mm, so that the bending length of the overall biological material is reduced by 50% after hydration for 10 minutes, and the overall thickness of the biological material remains unchanged. , the thicker the thickness of UBM, the lower the bending length and bending stiffness after hydration, and the better the operability.

Summary of clinical research protocol: a randomized, single-blind, parallel-controlled, multi-center clinical trial evaluating the effectiveness and safety of biological mesh in the treatment of abdominal wall hernia, with 150 subjects undergoing open surgery, including 75 cases in the test group and control group Group of 75 cases. The test device is sample A (test group), the control device is the reference product (porcine small intestinal submucosa product), the main observation index is the recurrence rate at 6 months after operation, and the secondary safety evaluation indexes are postoperative fever, hematoma/ Serous swelling, wound infection assessment, pain score, foreign body sensation in groin area, anaphylaxis.

Research result:

6-month recurrence rate

Test group: none.

Control group: 2 cases of recurrence.

18-month postoperative recurrence rate

Test group: none.

Control group: 4 cases of recurrence.

Other indicators:

The ease of operation of the patch in the test group was better than that in the control group, reflecting that the fixation time of the patch in the test group was shorter than that in the control group, which resulted in significantly shorter operation time than the control group.

Table 3 patch operation time

From the above clinical test results, it can be seen that the biological material of the present invention has a good operating feel as a whole, can maintain the stiffness of the material after hydration, has a good fit, facilitates surgical suturing operations, and shortens the fixation time of the patch.

The embodiments of the present invention have been described above in detail, but the present invention is not limited to the above embodiments. Even if various changes are made to the present invention, if these changes fall within the scope of the claims of the present invention and equivalent technologies, they still fall within the protection scope of the present invention.

Claims (7)

1. The biomaterial with the improved bending performance is characterized by comprising an acellular bladder basement membrane (UBM) and an acellular matrix, wherein the UBM completely covers the acellular matrix, the thickness of the UBM is 0.05-0.2mm, the acellular matrix is Small Intestinal Submucosa (SIS), dermis, pericardium, amnion and peritoneum, and the bending length of the biomaterial is reduced by not more than 50% after the biomaterial is completely hydrated for 10 min.

2. The biomaterial with improved bending properties according to claim 1, wherein the UBM is prepared from mammalian bladder by mechanical removal of serosa, muscular layer, submucosa, and muscularis mucosae followed by decellularization.

3. The biomaterial with improved bending properties according to claim 1, wherein the SIS is prepared by decellularization of the small mammalian intestine after mechanical removal of the mucosa, serosal layer and muscular layer.

4. The biomaterial with improved bending properties according to claim 1, further comprising a drug.

5. The biomaterial with improved bending properties according to claim 4, wherein the drug is distributed between or on the surface of the biomaterial or between and on the surface of the biomaterial via a medium.

6. The biomaterial with improved bending properties according to claim 1, wherein the biomaterial is fixed in a vacuum lamination manner.

7. The biomaterial with improved bending properties according to claim 6, wherein the process parameters of the vacuum lamination are: the vacuum pressure is-50 to-760 mmHg, and the action time is 0.5 to 72 hours.